Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLFIRI With Biomarker Stratification in Participants With Previously Untreated Metastatic Colorectal Cancer (mCRC) (MAVERICC)
30 de junho de 2016 atualizado por: Genentech, Inc.
MAVERICC (Marker Evaluation for Avastin Research in CRC): A Randomized Phase II Study of Bevacizumab+mFOLFOX6 Vs. Bevacizumab+FOLFIRI With Biomarker Stratification in Patients With Previously Untreated Metastatic Colorectal Cancer
This will be a randomized, open-label, multicenter, Phase II study with primary objectives to assess whether expression of select chemotherapy markers is associated with progression-free survival (PFS) in participants treated with bevacizumab plus leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) or bevacizumab plus leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI).
The study population will consist of participants with first-line mCRC.
Visão geral do estudo
Status
Concluído
Condições
Tipo de estudo
Intervencional
Inscrição (Real)
376
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Alberta
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Edmonton, Alberta, Canadá, T6G 1Z2
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
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Arkansas
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Little Rock, Arkansas, Estados Unidos, 72205-7199
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California
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Bellflower, California, Estados Unidos, 90706
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Duarte, California, Estados Unidos, 91010
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Fountain Valley, California, Estados Unidos, 92708
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Fresno, California, Estados Unidos, 93720
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Hayward, California, Estados Unidos, 94545
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Los Angeles, California, Estados Unidos, 90033
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Oakland, California, Estados Unidos, 94611
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Pleasant Hill, California, Estados Unidos, 94523
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Roseville, California, Estados Unidos, 95661
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Sacramento, California, Estados Unidos, 95817
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Sacramento, California, Estados Unidos, 95825
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San Francisco, California, Estados Unidos, 94115
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San Jose, California, Estados Unidos, 95119
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Santa Clara, California, Estados Unidos, 95051
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South San Francisco, California, Estados Unidos, 94080
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Vallejo, California, Estados Unidos, 94589
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Walnut Creek, California, Estados Unidos, 94596
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Colorado
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Denver, Colorado, Estados Unidos, 80218
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Connecticut
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Stamford, Connecticut, Estados Unidos, 06902
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Trumbull, Connecticut, Estados Unidos, 06611
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Florida
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Hollywood, Florida, Estados Unidos, 33021
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Jacksonville, Florida, Estados Unidos, 32256
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Miami, Florida, Estados Unidos, 33136
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Port Saint Lucie, Florida, Estados Unidos, 34952
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Idaho
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Boise, Idaho, Estados Unidos, 83712
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Illinois
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Joliet, Illinois, Estados Unidos, 60435
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Maywood, Illinois, Estados Unidos, 60153
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Peoria, Illinois, Estados Unidos, 61615
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Indiana
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Goshen, Indiana, Estados Unidos, 46526
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Indianapolis, Indiana, Estados Unidos, 46237
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Terre Haute, Indiana, Estados Unidos, 47802
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Kansas
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Fairway, Kansas, Estados Unidos, 66205
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Kentucky
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Elizabethtown, Kentucky, Estados Unidos, 42791
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Maine
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Scarborough, Maine, Estados Unidos, 04074
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Massachusetts
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Burlington, Massachusetts, Estados Unidos, 01805
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Montana
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Billings, Montana, Estados Unidos, 59102
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Nebraska
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Lincoln, Nebraska, Estados Unidos, 68506
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New Jersey
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Cherry Hill, New Jersey, Estados Unidos, 08003
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Manasquan, New Jersey, Estados Unidos, 08736
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New Mexico
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Albuquerque, New Mexico, Estados Unidos, 87131-5636
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Albuquerque, New Mexico, Estados Unidos, 87106
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Albuquerque, New Mexico, Estados Unidos, 87110
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Farmington, New Mexico, Estados Unidos, 87401
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Las Cruces, New Mexico, Estados Unidos, 88011
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Santa Fe, New Mexico, Estados Unidos, 87505
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New York
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Rochester, New York, Estados Unidos, 14642
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North Carolina
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Durham, North Carolina, Estados Unidos, 27710
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Greensboro, North Carolina, Estados Unidos, 27403
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High Point, North Carolina, Estados Unidos, 27262
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Washington, North Carolina, Estados Unidos, 27889
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Winston-salem, North Carolina, Estados Unidos, 27103
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Ohio
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Columbus, Ohio, Estados Unidos, 43219
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Toledo, Ohio, Estados Unidos, 43623
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73142
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Pennsylvania
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Dunmore, Pennsylvania, Estados Unidos, 18512
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Media, Pennsylvania, Estados Unidos, 19063
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Philadelphia, Pennsylvania, Estados Unidos, 19107
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Pittsburgh, Pennsylvania, Estados Unidos, 15212
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29414
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Texas
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Corpus Christi, Texas, Estados Unidos, 78404
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Houston, Texas, Estados Unidos, 77090
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53792
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Wauwatosa, Wisconsin, Estados Unidos, 53226
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Tallinn, Estônia, 13419
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Tartu, Estônia, 51014
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Cork, Irlanda
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Dublin, Irlanda, 24
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Galway, Irlanda
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Oslo, Noruega, 0407
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Coimbra, Portugal, 3000-075
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Lisboa, Portugal, 1649-035
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Porto, Portugal, 4200-072
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Aarau, Suíça, 5000
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Basel, Suíça, 4031
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Luzern, Suíça, 6004
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Zürich, Suíça, 8063
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Histologically or cytologically confirmed colorectal cancer (CRC) with at least one measurable metastatic lesion by RECIST Version 1.1
- Archival tumor tissue sample must be requested and available prior to study entry. If no archival tumor tissue sample is available, a fresh biopsy tissue sample must be obtained but should be discussed first with the medical monitor. A copy of the local pathology report must be submitted along with the specimens.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Participants with treated brain metastases are eligible for study participation. Participants may not receive ongoing treatment with steroids at Screening. Anticonvulsants (at stable dose) are allowed. Treatment for brain metastases may be whole-brain radiotherapy, radiosurgery, neurosurgery, or a combination as deemed appropriate by the treating physician. Radiotherapy and stereotactic radiosurgery must be completed at least 28 days prior to randomization.
- Female participants should not be pregnant or breastfeeding. Female participants with childbearing potential should agree to use effective, non-hormonal means of contraception during the study and for a period of at least 6 months following the last administration of study drugs. Female participants with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test within 7 days prior to randomization into the study.
- Male participants must agree to use effective contraception during the study and for a period of at least 6 months following the last administration of study drugs, even if they have been surgically sterilized.
Exclusion Criteria:
- Any prior systemic treatment for mCRC
- Adjuvant chemotherapy for CRC completed <12 months
- Evidence of Gilbert's syndrome or of homozygosity for the UGT1A1*28 allele
- Known positivity for human immunodeficiency virus (HIV)
- Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
- Radiotherapy to any site for any reason within 28 days prior to randomization, except for palliative radiotherapy to bone lesions within 14 days prior to randomization
- Clinically detectable third-space fluid collections that cannot be controlled by drainage or other procedures prior to study entry
- Treatment with any other investigational agent, or participation in another investigational drug trial within 28 days prior to randomization
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Bevacizumab + mFOLFOX6
Participants will receive bevacizumab plus mFOLFOX6 by intravenous (IV) infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity.
Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin, with bevacizumab continued in 3-week cycles.
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5-Fluorouracil 400 milligrams per meter-squared (mg/m^2) by IV bolus and subsequent 2400 mg/m^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Bevacizumab 5 milligrams per kilogram (mg/kg) of body weight via IV infusion will be administered every 2 weeks until disease progression or unacceptable toxicity.
If participants are discontinued from oxaliplatin or irinotecan due to unacceptable toxicity, bevacizumab may be given in 3-week cycles with capecitabine.
Outros nomes:
Leucovorin 400 mg/m^2 or dose deemed appropriate by Investigator via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Oxaliplatin 85 mg/m^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Capecitabine 850 or 1000 mg/m^2 may be offered in the event of unacceptable toxicity to oxaliplatin or irinotecan, to be given orally twice a day on Days 1 to 14 in 3-week cycles.
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Experimental: Bevacizumab + FOLFIRI
Participants will receive bevacizumab plus FOLFIRI by IV infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity.
Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan, with bevacizumab continued in 3-week cycles.
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5-Fluorouracil 400 milligrams per meter-squared (mg/m^2) by IV bolus and subsequent 2400 mg/m^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Bevacizumab 5 milligrams per kilogram (mg/kg) of body weight via IV infusion will be administered every 2 weeks until disease progression or unacceptable toxicity.
If participants are discontinued from oxaliplatin or irinotecan due to unacceptable toxicity, bevacizumab may be given in 3-week cycles with capecitabine.
Outros nomes:
Leucovorin 400 mg/m^2 or dose deemed appropriate by Investigator via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
Capecitabine 850 or 1000 mg/m^2 may be offered in the event of unacceptable toxicity to oxaliplatin or irinotecan, to be given orally twice a day on Days 1 to 14 in 3-week cycles.
Irinotecan 180 mg/m^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of largest diameters (LD) of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 millimeters (mm).
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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PFS According to RECIST Version 1.1 in Participants With High Vascular Endothelial Growth Factor (VEGF)-A Levels Versus Participants With Low VEGF-A Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and High VEGF-A Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and Low VEGF-A Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and High VEGF-A Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and Low VEGF-A Levels
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Overall Survival (OS)
Prazo: From Baseline until death (maximum up to 45 months overall)
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Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
OS was defined as the time from randomization to death.
The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death (maximum up to 45 months overall)
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OS in Participants With High ERCC-1 Levels
Prazo: From Baseline until death (maximum up to 45 months overall)
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Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
OS was defined as the time from randomization to death.
The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death (maximum up to 45 months overall)
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OS in Participants With Low ERCC-1 Levels
Prazo: From Baseline until death (maximum up to 45 months overall)
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Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
OS was defined as the time from randomization to death.
The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death (maximum up to 45 months overall)
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OS in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Prazo: From Baseline until death (maximum up to 45 months overall)
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Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
OS was defined as the time from randomization to death.
The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
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From Baseline until death (maximum up to 45 months overall)
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Percentage of Participants With Objective Response According to RECIST Version 1.1
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Objective response was defined as complete response (CR) or partial response (PR) according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to less than (<) 10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
The percentage of participants with CR or PR was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
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From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Objective response was defined as CR or PR according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
The percentage of participants with CR or PR was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Objective response was defined as CR or PR according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
The percentage of participants with CR or PR was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
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From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Objective response was defined as CR or PR according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
The percentage of participants with CR or PR was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Percentage of Participants With Disease Control According to RECIST Version 1.1
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Disease control was defined as CR, PR, or stable disease (SD) according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study.
The percentage of participants with CR, PR, or SD was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
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From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Disease control was defined as CR, PR, or SD according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study.
The percentage of participants with CR, PR, or SD was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
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From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Disease control was defined as CR, PR, or SD according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study.
The percentage of participants with CR, PR, or SD was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
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From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
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Disease control was defined as CR, PR, or SD according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study.
The percentage of participants with CR, PR, or SD was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
|
Percentage of Participants With Liver Metastasis Resection
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins.
In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1.
R2 was defined as macroscopic positive margins or incomplete resection at time of surgery.
The percentage of participants with resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Complete Liver Metastasis Resection
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins.
In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1.
R2 was defined as macroscopic positive margins or incomplete resection at time of surgery.
The percentage of participants with resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Liver Metastasis Resection in Participants With Low ERCC-1 Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins.
In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1.
R2 was defined as macroscopic positive margins or incomplete resection at time of surgery.
The percentage of participants with resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Complete Liver Metastasis Resection in Participants With Low ERCC-1 Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins.
In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1.
R2 was defined as macroscopic positive margins or incomplete resection at time of surgery.
The percentage of participants with resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
PFS According to RECIST Version 1.1 in Participants With Wild-Type V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Versus Participants With Mutant KRAS
Prazo: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Tumor assessments were performed according to RECIST Version 1.1.
Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm.
Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy.
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
PFS was defined as the time from randomization to death or disease progression, whichever occurred first.
The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
|
From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
|
OS in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Prazo: From Baseline until death (maximum up to 45 months overall)
|
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
OS was defined as the time from randomization to death.
The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
|
From Baseline until death (maximum up to 45 months overall)
|
|
OS in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS
Prazo: From Baseline until death (maximum up to 45 months overall)
|
Death on study included death from any cause occurring no later than 3 months after the last component of study treatment.
OS was defined as the time from randomization to death.
The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months.
The 95% CI was computed using the method of Brookmeyer and Crowley.
|
From Baseline until death (maximum up to 45 months overall)
|
|
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Objective response was defined as CR or PR according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
The percentage of participants with CR or PR was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
|
Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Objective response was defined as CR or PR according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
The percentage of participants with CR or PR was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
|
Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Prazo: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
Disease control was defined as CR, PR, or SD according to RECIST Version 1.1.
CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes.
PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline.
Confirmation of response at a consecutive assessment was not required.
SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study.
The percentage of participants with CR, PR, or SD was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
|
|
Percentage of Participants With Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins.
In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1.
R2 was defined as macroscopic positive margins or incomplete resection at time of surgery.
The percentage of participants with resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
|
Percentage of Participants With Complete Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
Prazo: At time of resective surgery during study (maximum up to 45 months overall)
|
The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator.
Resection was classified as R0, R1, or R2 following surgery.
R0 was defined as complete resection with clear margins ≥1 mm.
The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported.
The 95% CI was computed using normal approximation to the binomial distribution.
|
At time of resective surgery during study (maximum up to 45 months overall)
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Diretor de estudo: Christiane Langer, M.D., Genentech, Inc.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de agosto de 2011
Conclusão Primária (Real)
1 de maio de 2015
Conclusão do estudo (Real)
1 de julho de 2015
Datas de inscrição no estudo
Enviado pela primeira vez
14 de junho de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
15 de junho de 2011
Primeira postagem (Estimativa)
16 de junho de 2011
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
11 de agosto de 2016
Última atualização enviada que atendeu aos critérios de controle de qualidade
30 de junho de 2016
Última verificação
1 de junho de 2016
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Doenças do aparelho digestivo
- Neoplasias
- Neoplasias por local
- Neoplasias gastrointestinais
- Neoplasias do Aparelho Digestivo
- Doenças Gastrointestinais
- Doenças do cólon
- Doenças Intestinais
- Neoplasias Intestinais
- Doenças retais
- Neoplasias Colorretais
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Agentes de proteção
- Inibidores da Topoisomerase
- Agentes Antineoplásicos Imunológicos
- Inibidores de angiogênese
- Agentes Moduladores da Angiogênese
- Substâncias de crescimento
- Inibidores de crescimento
- Micronutrientes
- Vitaminas
- Inibidores da Topoisomerase I
- Antídotos
- Complexo de Vitamina B
- Fluorouracil
- Capecitabina
- Oxaliplatina
- Bevacizumabe
- Leucovorina
- Irinotecano
Outros números de identificação do estudo
- ML25710
- 2011-004755-39 (Número EudraCT)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .